Experimental Medications: NEW S1P Receptor Modulators

Ozanimod (RPC1063) is a selective modulator of one type of S1P receptor, S1P1. [Correction: Ozanimod is actually a selective modulator of two types of S1P receptors: S1P1 and S1P5. This note was added after publication.] It is given as a once-daily pill, and was studied in a Phase II trial called RADIANCE, where the experimental medicine was compared at two different doses with placebo. A total of 258 individuals with RRMS were studied in this trial, which began with a seven-day gradual titration of ozanimod up to the full dose under investigation. (Titration refers to starting with a lower dose and gradually increasing the dose until the full dose is reached. This helps to reduce the risk of side effects when starting a new medication.) The double-blind study ran for 24 weeks, followed by a yearlong safety-extension period.

At the end of the initial 24-week treatment period, patients in both groups taking ozanimod showed an 86 percent decrease in the cumulative number of gadolinium-enhanced lesions compared to the placebo group. The relapse rates also decreased in the treatment groups compared with placebo, with a 31 percent decrease in the 0.5 mg group and a 53 percent decrease in the 1 mg group.

The most common side effects reported were nasopharyngitis and headache. However, both of these events were reported more commonly in placebo-treated individuals compared with ozanimod-treated participants. Notably, no serious cardiac events, infections, or episodes of macular edema (a potential risk related to the eye for patients who take Gilenya) were reported in the subjects receiving ozanimod.19

In February 2016, the 72-week extension data of the RADIANCE trial were released. These showed a continued reduction in relapses and gadolinium-enhancing lesions for those individuals who remained on ozanimod, with all efficacy results favoring the 1 mg dose over the lower 0.5 mg dose. No new safety or tolerability issues were identified during this blinded extension phase of the trial.

The drug has moved into a larger, Phase III program with two trials that compare its efficacy against Avonex. The first trial, SUNBEAM, enrolled more than 1,300 patients in 20 countries who were followed for at least 12 months. Celgene reported that the trial was a success in February 2017, having met its primary endpoint of decreased relapse rate and its secondary endpoints of decreased lesion formation. The second trial is expected to run through the end of 2017.20, 21